Abstract

Over the past two decades there has been an increase in the incidence of obesity and metabolic diseases due to sedentary lifestyles, high caloric intake, genetics and environmental factors. Studies have shown that obesity is linked with multiple co-morbid pathologies, including increases in the incidence of some cancers. We have studied the effect of a nutrient-dense environment upon the mast cell, a pro-inflammatory immunocyte. Our recently published work shows that these immunocytes are sites for ectopic lipid deposition (steatosis) under conditions that mimic high nutrient availability and hyperinsulineamia. Moreover, the steatotic phenotype is associated with phenotypic change in the mast cells, with relative over-production of bioactive eicosanoids and other pro-inflammatory lipid mediators, but suppression of some aspects of the acute Type I hypersensitivity pathway. In the current study we sought to further explore the impact of nutrient abundance upon the cell biology of the mast cell. We observe the induction of ER stress pathways, which is associated with the re-programming of the ER towards lipid synthesis and deposition in lipid bodies. Moreover, we observe the induction of autophagy pathways, which likely reflect cellular attempts to access the dysregulated ER and lipid bodies in an effort to return to homeostasis. These studies deepen our understanding of the degree to which altered nutrient environments can, in turn, cause immunological dysregulation. Of particular interest for future studies will be the links between mast cell dysregulation and the systemic and local inflammatory pathology that is associated with metabolic syndrome.